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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:154.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Microarray Analysis Reveals Overexpression of CD163 and HO-1 in Symptomatic Carotid Plaques

Petra Ijäs; Krista Nuotio; Jani Saksi; Lauri Soinne; Eija Saimanen; Marja-Liisa Karjalainen-Lindsberg; Oili Salonen; Seppo Sarna; Jarno Tuimala; Petri T. Kovanen; Markku Kaste; Perttu J. Lindsberg

From the Departments of Neurology (P.I., K.N., L.S., M.K., P.J.L.), Surgery (E.S.), Pathology (M.-L.K.-L.), and Radiology (O.S.), Helsinki University Central Hospital; the Neuroscience Program (P.I., K.N., J.S., P.J.L.), Biomedicum Helsinki; South Karelia Central Hospital (E.S.), Lappeenranta; the Department of Public Health (S.S.), University of Helsinki; CSC - Scientific Computing Ltd (J.T.), Espoo; and Wihuri Research Institute (P.T.K.), Helsinki, Finland.

Correspondence to Petra Ijäs, Department of Neurology, Biomedicum Helsinki, P.O.Box 700 (Haartmaninkatu 8, Room B411b), FI-00029 HUS, Finland. E-mail petra.ijas{at}hus.fi

Objective— We studied by microarray analysis whether symptomatic and asymptomatic carotid plaques from the same patient differ in gene expression and whether the same changes are present in an independent sample set.

Methods and Results— Carotid plaques from four patients with bilateral high-grade stenosis, one being symptomatic and the other asymptomatic, were analyzed on Affymetrix U95Av2 arrays. 33 genes showed >1.5-fold change between symptomatic and asymptomatic plaques in an intraindividual comparison with FDR ranging from 0.28 to 0.40. Three genes involved in iron-heme homeostasis, CD163, HO-1, and transferrin receptor, were further analyzed in 40 independent plaques. HO-1 (fold-change 1.93, 95%CI 1.04 to 3.94, P=0.040) and CD163 (1.58, 1.11 to 2.40, P=0.013) mRNAs were again induced, and also HO-1 protein was overexpressed in symptomatic plaques (4.38, 1.54 to 12.20, P=0.024). The expression of HO-1 and CD163 correlated with tissue iron content but iron itself was not associated with the symptom status.

Conclusions— Symptomatic plaques show overexpression of CD163 and HO-1 both in intraindividual and interindividual comparison. Their expression correlates with iron deposits but asymptomatic and symptomatic plaques from isolated patients do not differ in macroscopic hemorrhages or iron deposits. We suggest that symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages.

We showed that HO-1 and CD163 were overexpressed in symptomatic carotid plaques. Their expression correlated with iron deposition but iron itself was not associated with symptom status. Symptomatic plaques might show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages.

Key Words: atherosclerosis • carotid arteries • gene expression • microarray • stroke

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